Evolution of Blindness in Cavefish

The fish species Astyanax mexicanus exists in a form that exists above ground and has normal eyes and in forms that exist in caves (cavefish), which are blind and undergo degeneration of the eye. In evolutionary terms, the loss of the eye might simply reflect lack of selection for eyesight in cavefish. However, Yamamoto et al. present evidence that, instead, eye degeneration appears to have been derived as an adaptive trait driven by natural selection. Critical signals for eye development come from the cells of the anterior embryonic midline in the form of so-called hedgehog (Hh) proteins. In cavefish, eye primordia form but stop developing and degenerate. This phenotype appears to arise not from failure of Hh signaling, but rather from increased expression of Hh proteins in the developing cavefish embryo. Increased Hh signaling in wild-type embryos (induced by injection of mRNA encoding Hh proteins) produced adults that lacked an eye. Application of a pharmacological inhibitor of Hh signaling in cavefish partly restored development of the eye. It is estimated that loss of the eye probably results from modification of four to six genes. The authors suggest that changes in genes encoding Hh proteins or other genes that regulate the Hh pathway further upstream may represent these critical events.